NM_002747.4:c.547-188C>A

Variant names:

• chr18-50714891-C-A
• rs3752088
• NM_002747.4:c.547-188C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002747.4(MAPK4):​c.547-188C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,968 control chromosomes in the GnomAD database, including 20,567 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20567 hom., cov: 32)
• Consequence: MAPK4 NM_002747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545
• Publications: 3 publications found

Genes affected

MAPK4 (HGNC:6878): (mitogen-activated protein kinase 4) Mitogen-activated protein kinase 4 is a member of the mitogen-activated protein kinase family. Tyrosine kinase growth factor receptors activate mitogen-activated protein kinases which then translocate into the nucleus and phosphorylate nuclear targets. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK4	NM_002747.4	c.547-188C>A		intron_variant	Intron 2 of 5	ENST00000400384.7	NP_002738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK4	ENST00000400384.7	c.547-188C>A		intron_variant	Intron 2 of 5	1	NM_002747.4	ENSP00000383234.1
MAPK4	ENST00000592595.5	c.547-188C>A		intron_variant	Intron 2 of 3	1		ENSP00000466233.1
MAPK4	ENST00000540640.3	c.-87-188C>A		intron_variant	Intron 1 of 4	2		ENSP00000439231.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78090 AN: 151850 Hom.: 20545 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.517

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.514 AC: 78128 AN: 151968 Hom.: 20567 Cov.: 32 AF XY: 0.518 AC XY: 38447 AN XY: 74268

African (AFR) AF: 0.486 AC: 20115 AN: 41408

American (AMR) AF: 0.629 AC: 9593 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1760 AN: 3470

East Asian (EAS) AF: 0.797 AC: 4118 AN: 5164

South Asian (SAS) AF: 0.623 AC: 2996 AN: 4808

European-Finnish (FIN) AF: 0.458 AC: 4840 AN: 10576

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33024 AN: 67978

Other (OTH) AF: 0.521 AC: 1097 AN: 2104

Alfa AF: 0.500 Hom.: 29413

Bravo AF: 0.528

Asia WGS AF: 0.733 AC: 2544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3752088; hg19: chr18-48241261;